Bucy R P
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Immunopharmacology. 1988 Mar-Apr;15(2):65-72. doi: 10.1016/0162-3109(88)90053-7.
The immune system is regulated by the interactions among several distinct functional subsets of T cells. The action of several commonly used immunosuppressive drugs on the activation of cytotoxic T lymphocytes (CTL) and suppressor T lymphocytes (Ts) in the primary mixed lymphocyte reaction (MLR) was investigated. Cyclosporin A, hydrocortisone, and azathioprine were all found to inhibit both CTL and Ts activation when present at pharmacological doses in culture. When these drug-inhibited cultures were reconstituted with interleukin-2, however, clear differences between the effects of these drugs was observed. Cyclosporin A and hydrocortisone allowed the selective activation of Ts in the presence of interleukin-2, while azathioprine inhibition was not reversed by interleukin-2. Thus, CTL precursors appear to be directly inhibited by all of these drugs, but Ts precursors apparently are not inhibited by cyclosporin A or hydrocortisone provided interleukin-2 is present. These findings are discussed in terms of the activation requirements of CTL vs. Ts and the implications of the selective activation of alloantigen-specific Ts for prevention of allograft rejection.
免疫系统受几种不同功能的T细胞亚群间相互作用的调节。研究了几种常用免疫抑制药物在初次混合淋巴细胞反应（MLR）中对细胞毒性T淋巴细胞（CTL）和抑制性T淋巴细胞（Ts）激活的作用。当在培养中以药理剂量存在时，环孢素A、氢化可的松和硫唑嘌呤均被发现可抑制CTL和Ts的激活。然而，当用白细胞介素-2重建这些药物抑制的培养物时，观察到了这些药物作用之间的明显差异。在白细胞介素-2存在的情况下，环孢素A和氢化可的松可使Ts选择性激活，而硫唑嘌呤的抑制作用不能被白细胞介素-2逆转。因此，CTL前体似乎被所有这些药物直接抑制，但如果存在白细胞介素-2，Ts前体显然不会被环孢素A或氢化可的松抑制。根据CTL与Ts的激活要求以及同种异体抗原特异性Ts的选择性激活对预防同种异体移植排斥反应的意义对这些发现进行了讨论。
